Patent Watch

June 20, 2011

Make pheromones and fragrances from alkenyl isobutyrates. Inventors R. H. Bedoukian and L. C. Passaro prepared compounds that act as pheromones to help combat insects that damage fruit trees. Some of these compounds are also useful as fragrances. The inventors wanted to devise a method for producing the desired compounds with a high transisomer content because this configuration is usually more effective for pheromones. Other synthetic methods are available, but improvements in the yields of trans isomers are necessary.

The route used to prepare synthetic pheromones such as 1 is outlined in the figure. The first step is to convert chloroacetal 2 to Grignard reagent 3, which is then treated with isobutyrate ester 4 in the presence of a copper catalyst such as LiCuBr2. Acetal product 5 is treated with HCO2H to give 1 in 94% isolated yield and an E/Z ratio of 76:24.

The key to achieving high trans content in the product is to ensure that starting compound 2 or, preferably, the copper catalyst contains a bromine atom. About 4 mol% of catalyst is used; it is preferable to combine it with ester 4 before adding the Grignard reagent. If 4 is an ester of an acid containing at least four carbon atoms, the overall product yield is higher than when an acid with fewer carbon atoms is used.

The patent’s claims cover the preparation of several specific compounds with this procedure, and the examples cover five of these. In place of acetal 2, the starting material can be an alcohol or tetrahydropyranyl derivative and the isobutyrate ester can have an ethyl or n-butyl group in place of one of the vinyl groups. The process gives high yields of the desired trans isomers of these products. (Bedoukian Research [Danbury, CT]. US Patent 7,932,410, April 26, 2011; Keith Turner)